Metabolic plasticity in CLL: adaptation to the hypoxic niche.

Koczula, K M, Ludwig, C, Hayden, R, Cronin, L, Pratt, Guy, Parry, H, Tennant, D, Drayson, M, Bunce, C M, Khanim, F L and Günther, U L (2016) Metabolic plasticity in CLL: adaptation to the hypoxic niche. Leukemia, 30 (1). pp. 65-73. ISSN 1476-5551. This article is available to all HEFT staff and students via http://tinyurl.com/z795c8c by using their HEFT Athens login IDs

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Abstract

Metabolic transformation in cancer is increasingly well understood. However, little is known about the metabolic responses of cancer cells that permit their survival in different microenvironments. We have used a nuclear magnetic resonance based approach to monitor metabolism in living primary chronic lymphoid leukemia (CLL) cells and to interrogate their real-time metabolic responses to hypoxia. Our studies demonstrate considerable metabolic plasticity in CLL cells. Despite being in oxygenated blood, circulating CLL cells are primed for hypoxia as measured by constitutively low level hypoxia-inducible factor (HIF-1α) activity and modest lactate production from glycolysis. Upon entry to hypoxia we observed rapid upregulation of metabolic rates. CLL cells that had adapted to hypoxia returned to the 'primed' state when re-oxygenated and again showed the same adaptive response upon secondary exposure to hypoxia. We also observed HIF-1α independent differential utilization of pyruvate in oxygenated and hypoxic conditions. When oxygenated, CLL cells released pyruvate, but in hypoxia imported pyruvate to protect against hypoxia-associated oxidative stress. Finally, we identified a marked association of slower resting glucose and glutamine consumption, and lower alanine and lactate production with Binet A0 stage samples indicating that CLL may be divided into tumors with higher and lower metabolic states that reflect disease stage.

Item Type:	Article
Additional Information:	This article is available to all HEFT staff and students via http://tinyurl.com/z795c8c by using their HEFT Athens login IDs
Subjects:	QZ Pathology. Oncology WH Haemic and lymphatic systems. Haematology
Divisions:	Planned IP Care > Oncology and Clinical Haematology
Related URLs:	https://www.ncbi.nlm.nih.gov/pubmed/2620...
Depositing User:	Mrs Caroline Tranter
Date Deposited:	10 Feb 2017 09:57
Last Modified:	10 Feb 2017 09:57
URI:	http://www.repository.uhblibrary.co.uk/id/eprint/1180

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